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Culture Syndrome

Kavitha Siva, Fredrik Ek, Jun Chen, Abdul Ghani Alattar, Kristmundur Sigmundsson, Roger Olsson, Marcin Wlodarski, Thomas Lundbäck, Johan Flygare
Diamond-Blackfan anemia (DBA) is a bone marrow failure syndrome caused by mutations in ribosomal protein genes. Pathogenic mechanisms are poorly understood but involve severely reduced proliferation of erythroid precursors. Because current DBA therapies are ineffective and associated with severe side effects, disease-specific therapies are urgently needed. We hypothesized that druggable molecular pathways underlying the defect can be revealed through phenotypic small-molecule screens. Accordingly, a screening assay was developed using c-kit+ fetal liver erythroid progenitors from a doxycycline-inducible DBA mouse model...
March 2019: SLAS Discovery
Jinghe Cao, Gulijianati Maowulieti, Tao Yu
Expression of peroxisome proliferator-activated receptor γ (PPARγ) mRNA in ovarian granulosa cells of patients with polycystic ovary syndrome (PCOS) were explored. Ovarian granulosa cells were extracted from 5 patients with PCOS and 30 normal controls. Expression of PPARγ mRNA in granulosa cells of the 5 PCOS patients (observation group) and 5 normal controls (control group) was detected by RT-qPCR. The remaining 25 cases of normal human ovarian granulosa cells were cultured in vitro for 48 h, followed by cell culture for another 24 h with different concentrations of testosterone, insulin (INS), and rosiglitazone (RGZ)...
March 2019: Experimental and Therapeutic Medicine
Qin Wang, Derun Wang, Shigeru Shibata, Tianrong Ji, Lei Zhang, Rui Zhang, He Yang, Linlin Ma, Jundong Jiao
Researches have shown that mice lacking the metabotropic glutamate receptor 1 (mGluR) showed albuminuria, remodeling of F-actin, with loss of stress fibers. Selective group I mGluRs agonist (S)-3,5-dihydroxyphenylglycine (DHPG) attenuated albuminuria in several rodent models of nephrotic syndrome. However, the molecular mechanism is obscure. Using a human podocyte cell line, we here investigated the molecular mechanisms of group I mGluRs-induced calcium influx and the formation of stress fibers. Our data showed that group I mGluRs activation by DHPG induced a significant calcium influx, and promoted cytoskeletal stress fiber formation and focal adhesions in podocytes...
February 16, 2019: Biochemical and Biophysical Research Communications
Ioana Bratu, Kurt Heiss, Claudia Mueller, Andrea Winthrop, Geoffrey Blair, Carol-Anne Moulton
The following is a summary of the fourth Ein Panel Debate Session from the 50th Annual Meeting of the Canadian Association of Pediatric Surgeons (CAPS) held in Toronto, ON, from September 26-29, 2018. The session focused on surgeon well-being at different stages of career: role of mentorship at the start of career, second victim syndrome, litigation stress syndrome, and retirement. Using Maslach Burnout Inventory Survey, CAPS members were presented their wellness scores as a group compared to other health care providers...
January 31, 2019: Journal of Pediatric Surgery
S Paries, S Funcke, O Kershaw, K Failing, M Lierz
Tortoise Picornavirus (ToPV) commonly known as Virus "X" was recently discovered in juvenile European tortoises suffering from soft carapace and plastron as well as kidney disease. Therefore, this virus was a potential candidate to be a causative agent for these disease patterns. Spur thighed tortoises (Testudo graeca) seemed to be more susceptible to establish clinical symptoms than other European species like T. hermanni. Thus this trial investigated the role of ToPV in the described syndrome. Two groups of juvenile European tortoises (T...
2019: PloS One
D Tolomeo, A Rubegni, M Severino, F Pochiero, C Bruno, D Cassandrini, A Madeo, S Doccini, M Pedemonte, A Rossi, F D'Amore, M A Donati, M Di Rocco, F M Santorelli, C Nesti
Complex I (CI) is the largest component of the mitochondrial respiratory chain (MRC) and it is made up of 7 mitochondrial DNA (mtDNA)-encoded and at least 38 nuclear DNA-encoded subunits. Isolated CI deficiency is the most common single enzyme deficiency in the heterogeneous group of MRC disorders and it is a relatively common etiology of Leigh-like syndrome (LS). With a few exceptions, descriptions of the clinical spectrum of specific mutations in CI are scarce. We here present three unrelated Italian children who harbored the homoplasmic m...
February 6, 2019: Journal of the Neurological Sciences
Supram Hosuru Subramanya, Rajesh Amberpet, Dinesh Chaudhary, Niranjan Nayak, Shashiraja Padukone, Indira Bairy, Shishir Gokhale
Background: Vancomycin-resistant enterococcal infections in the neonatal ICU are growing global problems. We report a case of neonatal septicemia by multidrug-resistant vancomycin-resistant Enterococcus faecium (VRE), the source of infection being the mother's gut. Case presentation: A newborn male child admitted to the neonatal intensive care unit (NICU) was diagnosed to have mild meconium aspiration syndrome, early onset neonatal septicemia, and bacteremia by multidrug and vancomycin-resistant Enterococcus faecium ...
2019: Antimicrobial Resistance and Infection Control
Yohei Korogi, Shimpei Gotoh, Satoshi Ikeo, Yuki Yamamoto, Naoyuki Sone, Koji Tamai, Satoshi Konishi, Tadao Nagasaki, Hisako Matsumoto, Isao Ito, Toyofumi F Chen-Yoshikawa, Hiroshi Date, Masatoshi Hagiwara, Isao Asaka, Akitsu Hotta, Michiaki Mishima, Toyohiro Hirai
It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. From an HPS type 2 (HPS2) patient, we established disease-specific iPSCs (HPS2-iPSCs) and their gene-corrected counterparts...
January 30, 2019: Stem Cell Reports
Bryce D Warren, Soo H Ahn, Lynda K McGinnis, Geoffrey Grzesiak, Ren-Wei Su, Asgi T Fazleabas, Lane K Christenson, Brian K Petroff, Margaret G Petroff
Autoimmune Regulator (AIRE) regulates central immune tolerance by inducing expression of tissue-restricted antigens in thymic medullary epithelial cells, thereby ensuring elimination of autoreactive T cells. Aire mutations in humans and targeted Aire deletion in mice results in multi-organ autoimmune disease, known in humans as Autoimmune Polyglandular Syndrome Type 1 (APS-1). APS-1 is characterized by presence of adrenal insufficiency, chronic mucosal candidiasis, and/or hypoparathyroidism. Additionally, females often present with gonadal insufficiency and infertility...
February 16, 2019: Biology of Reproduction
Jacek Szymański, Kornelia Zaręba, Grzegorz Jakiel, Aneta Słabuszewska-Jóźwiak
Vulvovaginal atrophy accompanied by lower urinary tract dysfunction related to low levels of estrogen and androgens is labeled as genitourinary syndrome of menopause (GSM). Although this condition affects most postmenopausal women worldwide, it seems to be underdiagnosed and undertreated. Women should be properly advised to choose an adequate treatment modality to improve their quality of life, sexual relationships and social activity. The aim of this article to is increase knowledge of GSM. The current treatment options, both hormonal and non-hormonal, are reviewed...
December 2018: Przeglad Menopauzalny, Menopause Review
Jakub Malinowski, Miłosz Wilczyński, Adam Depta, Andrzej Malinowski
Vulvovaginal atrophy accompanied by lower urinary tract dysfunction related to low levels of estrogen and androgens is labeled as genitourinary syndrome of menopause (GSM). Although this condition affects most postmenopausal women worldwide, it seems to be underdiagnosed and undertreated. Women should be properly advised to choose an adequate treatment modality to improve their quality of life, sexual relationships and social activity. The aim of this article is to increase knowledge of GSM. The current treatment options, both hormonal and non-hormonal, are reviewed...
December 2018: Przeglad Menopauzalny, Menopause Review
Nisha K Duggal, Erin M McDonald, James Weger-Lucarelli, Seth A Hawks, Jana M Ritter, Hannah Romo, Gregory D Ebel, Aaron C Brault
Zika virus (ZIKV) infection can result in neurological disorders including Congenital Zika Syndrome in infants exposed to the virus in utero. Pregnant women can be infected by mosquito bite as well as by sexual transmission from infected men. Herein, the variants of ZIKV within the male reproductive tract and ejaculates were assessed in inoculated mice. We identified two non-synonymous variants at positions E-V330L and NS1-W98G. These variants were also present in the passage three PRVABC59 isolate and infectious clone relative to the patient serum PRVABC59 sequence...
February 7, 2019: Virology
Emilie Lalonde, Jessica Ebrahimzadeh, Keith Rafferty, Jennifer Richards-Yutz, Richard Grant, Erik Toorens, Jennifer Marie Rosado, Erica Schindewolf, Tapan Ganguly, Jennifer M Kalish, Matthew A Deardorff, Arupa Ganguly
BACKGROUND: Somatic overgrowth conditions, including Proteus syndrome, Sturge-Weber syndrome, and PIK3CA-related overgrowth spectrum, are caused by post-zygotic pathogenic variants, result in segmental mosaicism, and give rise to neural, cutaneous and/or lipomatous overgrowth. These variants occur in growth-promoting pathways leading to cellular proliferation and expansion of tissues that arise from the affected cellular lineage. METHODS: We report on 80 serial patients evaluated for somatic overgrowth conditions in a diagnostic laboratory setting, including three prenatal patients...
February 13, 2019: Molecular Genetics & Genomic Medicine
Felipe J Núñez, Flor M Mendez, Padma Kadiyala, Mahmoud S Alghamri, Masha G Savelieff, Maria B Garcia-Fabiani, Santiago Haase, Carl Koschmann, Anda-Alexandra Calinescu, Neha Kamran, Meghna Saxena, Rohin Patel, Stephen Carney, Marissa Z Guo, Marta Edwards, Mats Ljungman, Tingting Qin, Maureen A Sartor, Rebecca Tagett, Sriram Venneti, Jacqueline Brosnan-Cashman, Alan Meeker, Vera Gorbunova, Lili Zhao, Daniel M Kremer, Li Zhang, Costas A Lyssiotis, Lindsey Jones, Cameron J Herting, James L Ross, Dolores Hambardzumyan, Shawn Hervey-Jumper, Maria E Figueroa, Pedro R Lowenstein, Maria G Castro
Patients with glioma whose tumors carry a mutation in isocitrate dehydrogenase 1 (IDH1R132H ) are younger at diagnosis and live longer. IDH1 mutations co-occur with other molecular lesions, such as 1p/19q codeletion, inactivating mutations in the tumor suppressor protein 53 (TP53 ) gene, and loss-of-function mutations in alpha thalassemia/mental retardation syndrome X-linked gene ( ATRX ). All adult low-grade gliomas (LGGs) harboring ATRX loss also express the IDH1R132H mutation. The current molecular classification of LGGs is based, partly, on the distribution of these mutations...
February 13, 2019: Science Translational Medicine
Qiujun Yu, Yi-Yin Tai, Ying Tang, Jingsi Zhao, Vinny Negi, Miranda K Culley, Jyotsna Pilli, Wei Sun, Karin Brugger, Johannes Mayr, Rajeev Saggar, Rajan Saggar, W Dean Wallace, David J Ross, Aaron B Waxman, Stacy G Wendell, Steven J Mullett, John Sembrat, Mauricio Rojas, Omar F Khan, James E Dahlman, Masataka Sugahara, Nobuyuki Kagiyama, Taijyu Satoh, Manling Zhang, Ning Feng, John Gorcsan Iii, Sara O Vargas, Kathleen J Haley, Rahul Kumar, Brian B Graham, Robert Langer, Daniel G Anderson, Bing Wang, Sruti Shiva, Thomas Bertero, Stephen Y Chan
BACKGROUND: Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. The BolA Family Member 3 (BOLA3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined. METHODS: In vitro assessment of BOLA3 regulation and gain and loss of function assays were performed in human pulmonary artery endothelial cells (PAECs) using siRNA and lentiviral vectors expressing the mitochondrial isoform of BOLA3...
February 14, 2019: Circulation
Sandeep Silawal, Maximilian Willauschus, Gundula Schulze-Tanzil, Clemens Gögele, Markus Geßlein, Silke Schwarz
The association between osteoarthritis (OA), obesity and metabolic syndrome suggests an interrelation between OA and diabetes mellitus (DM). Little is known about the role of anti-inflammatory cytokine interleukin (IL)-10 in the interrelation between OA and DM. Hence, the effects of IL-10 under hyperglycemia (HG) and hyperinsulinemia (HI) in human articular chondrocytes (hAC) and chondrosarcoma cell line Okayama University Medical School (OUMS)-27 were examined. HAC and OUMS-27, cultured in normoglycemic (NG) and HG conditions were stimulated with insulin and/or IL-10...
February 12, 2019: International Journal of Molecular Sciences
Mahmoud Mona, Rehae Miller, Hui Li, Yun-Jong Park, Raafi Zaman, Li-Jun Yang, Seunghee Cha
Sjögren's syndrome (SjS) is an autoimmune disease that destroys the salivary glands and results in severe dry mouth. Mesenchymal stem cell (MSC) transplantation has been recently proposed as a promising therapy for restoring cells in multiple degenerative diseases. We have recently utilized advanced proteomics biochemical assays to identify the key molecules involved in the mesenchymal-epithelial transition (MET) of co-cultured mouse bone-marrow-derived MSCs mMSCs with primary salivary gland cells. Among the multiple transcription factors (TFs) that were differentially expressed, two major TFs were selected: muscle, intestine, and stomach expression-1 (MIST1) and transcription factor E2a (TCF3)...
February 12, 2019: International Journal of Molecular Sciences
Yohannes Tesfaigzi, Hans Petersen, Bartolome Celli, Caroline Owen
Chronic obstructive pulmonary disease (COPD) is a syndrome that comprises several lung pathologies, but subphenotyping the various disease subtypes has not been successful. We found that a single-nucleotide polymorphism (SNP) within the proline-rich domain of transformation-related protein 53 (TP53) that modifies Pro72 to Arg is associated with twofold increased risk for chronic bronchitis in the Lovelace Smokers and COPDGene cohorts. This association is pronounced for those who report either wood smoke, dust, or fumes exposure...
December 2018: Annals of the American Thoracic Society
Hadri Hadi Yusof, Han-Chung Lee, Eryse Amira Seth, Xiangzhong Wu, Chelsee A Hewitt, Hamish S Scott, Pike-See Cheah, Yue-Ming Li, De-Ming Chau, King-Hwa Ling
Notch signalling pathway is involved in the proliferation of neural progenitor cells (NPCs), to inhibit neuronal cell commitment and to promote glial cell fate. Notch protein is cleaved by gamma-secretase, a multisubunit transmembrane protein complex that releases the Notch intracellular domain (NICD) and subsequently activates the downstream targets. Down syndrome (DS) individuals exhibit an increased number of glial cells (particularly astrocytes), and reduced number of neurons suggesting the involvement of Notch signalling pathway in the neurogenic-to-gliogenic shift in DS brain...
February 13, 2019: Journal of Molecular Neuroscience: MN
Satoshi Yoshida, Ryoji Takazawa, Yusuke Uchida, Yusuke Kohno, Yuma Waseda, Toshihiko Tsujii
We examined the renal pelvic urine culture (RPUC) and stone culture (SC) during ureteroscopy and evaluated their associations with postoperative systemic inflammatory response syndrome (SIRS). We prospectively collected data of 224 patients who underwent ureteroscopic laser lithotripsy from March 2015 to December 2017. We examined the bladder urine culture pre-operatively. If the patients had positive culture results, we treated them with antibiotics for 5-7 days before surgery based on the sensitivity profile...
February 13, 2019: Urolithiasis
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